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Article ; Online: The effect of pre-analytical variables on downstream application and data analysis of human endometrial biopsies.

Maclean, A / Adishesh, M / Button, L / Richards, L / Alnafakh, R / Newton, E / Drury, J / Hapangama, D K

Human reproduction open

2022 Volume 2022, Issue 3, Page(s) hoac026

Abstract: Study question: What are the effects of pre-analytical variables on the downstream analysis of patient-derived endometrial biopsies?: Summary answer: There are distinct differences in the protein levels of the master regulator of oxygen homeostasis, ... ...

Abstract	Study question: What are the effects of pre-analytical variables on the downstream analysis of patient-derived endometrial biopsies? Summary answer: There are distinct differences in the protein levels of the master regulator of oxygen homeostasis, hypoxia-inducible factor-1-alpha (HIF1α), and the protein and mRNA levels of three related genes, carbonic anhydrase 9 ( What is known already: Patient-derived biopsies are vital to endometrial research, but pre-analytical variables relating to their collection may affect downstream analysis, as is evident in other tissues. Study design size duration: A prospective observational study including patients undergoing hysterectomy for endometrial cancer (EC) or benign indications was conducted at a large tertiary gynaecological unit in the UK. Endometrial biopsies were obtained at different time points (pre- or post-hysterectomy) using either a pipelle endometrial sampler or as a full-thickness wedge biopsy. Participants/materials setting methods: The changes in HIF1α, CA9, VEGFA and PR protein levels were measured by semi-quantitative analysis of immunostaining, and the expression levels of three genes ( Main results and the role of chance: An increase in HIF1α immunostaining was observed in EC versus benign endometrium (functionalis glands) obtained pre-hysterectomy ( Large scale data: N/A. Limitations reasons for caution: This descriptive study explores the effect of pre-analytical variables on the expression of four proteins and three hypoxia-related genes in a limited number of endometrial biopsies from patients with EC and benign controls. Due to the small number, it was not possible to investigate other potential variables such as menstrual cycle phase, region-specific differences within the endometrium, grade and stage of cancer, and surgical technicalities. Wider implications of the findings: Careful consideration of the effects of these pre-analytical variables is essential when interpreting data relating to human endometrial biopsies. A standardized approach to endometrial tissue collection is essential to ensure accurate and clinically transferrable data. Study funding/competing interests: The authors have no conflicts of interest to declare. The work included in this manuscript was funded by Wellbeing of Women project grants RG1073 and RG2137 (D.K.H.), Wellbeing of Women Entry-Level Scholarship ELS706 and Medical Research Council MR/V007238/1 (A.M./D.K.H.), Liverpool Women's Hospital Cancer Charity (M.A.) and University of Liverpool (L.B., L.R. and E.N.).
Language	English
Publishing date	2022-06-13
Publishing country	England
Document type	Journal Article
ISSN	2399-3529
ISSN (online)	2399-3529
DOI	10.1093/hropen/hoac026
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Article: Enriching Personalized Endometrial Cancer Research with the Harmonization of Biobanking Standards.

Adishesh, Meera / Hapangama, Dharani K

Cancers

2019 Volume 11, Issue 11

Abstract: Endometrial cancer is the commonest gynecological cancer, with an incidence predicted to escalate by a further 50-100% before 2025, due to the rapid rise in risk factors such as obesity and increased life expectancy. Endometrial cancer associated ... ...

Abstract	Endometrial cancer is the commonest gynecological cancer, with an incidence predicted to escalate by a further 50-100% before 2025, due to the rapid rise in risk factors such as obesity and increased life expectancy. Endometrial cancer associated mortality is also rising, depicting the need for translatable research to improve our understanding of the disease. Rapid translation of scientific discoveries will facilitate the development of new diagnostic, prognostic and therapeutic strategies. Biobanks play a vital role in providing biospecimens with accompanying clinical data for personalized translational research. Wide variation in collection, and pre-analytic variations in processing and storage of bio-specimens result in divergent and irreproducible data from multiple studies that are unsuitable for collation to formulate robust conclusions. Harmonization of biobanking standards is thus vital, in facilitating international multi-center collaborative studies with valuable outcomes to improve personalized treatments. This review will detail the pitfalls in the biobanking of biosamples from women with cancer in general, and describe the recent international harmonization project that developed standardized research tools to overcome these challenges and to enhance endometrial cancer research, which will facilitate future development of personalized novel diagnostic strategies and treatments.
Language	English
Publishing date	2019-11-05
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers11111734
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Article: Endometriosis of the liver.

Adishesh, M / Hawarden, A / Rowlands, D

British journal of hospital medicine (London, England : 2005)

2016 Volume 77, Issue 5, Page(s) 310–311

MeSH term(s)	Endometriosis/diagnosis ; Endometriosis/surgery ; Female ; Humans ; Liver Diseases/diagnosis ; Young Adult
Language	English
Publishing date	2016-05
Publishing country	England
Document type	Case Reports ; Journal Article
ISSN	1750-8460
ISSN	1750-8460
DOI	10.12968/hmed.2016.77.5.310
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Article: Human Uterine Biopsy: Research Value and Common Pitfalls.

Maclean, Alison / Kamal, Areege / Adishesh, Meera / Alnafakh, Rafah / Tempest, Nicola / Hapangama, Dharani K

International journal of reproductive medicine

2020 Volume 2020, Page(s) 9275360

Abstract: The human uterus consists of the inner endometrium, the myometrium, and the outer serosa. Knowledge of the function of the uterus in health and disease is relevant to reproduction, fertility, embryology, gynaecology, endocrinology, and oncology. Research ...

Abstract	The human uterus consists of the inner endometrium, the myometrium, and the outer serosa. Knowledge of the function of the uterus in health and disease is relevant to reproduction, fertility, embryology, gynaecology, endocrinology, and oncology. Research performed on uterine biopsies is essential to further the current understanding of human uterine biology. This brief review explores the value of the uterine biopsy in gynaecological and human fertility research and explores the common problems encountered when analysing data generated from different types of uterine biopsies, with the aim of improving the quality, reproducibility, and clinical translatability of future research.
Language	English
Publishing date	2020-04-28
Publishing country	Egypt
Document type	Journal Article ; Review
ISSN	2356-7104
ISSN	2356-7104
DOI	10.1155/2020/9275360
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Article: Endometriosis Is Associated with a Significant Increase in hTERC and Altered Telomere/Telomerase Associated Genes in the Eutopic Endometrium, an Ex-Vivo and In Silico Study.

Alnafakh, Rafah / Choi, Fiona / Bradfield, Alice / Adishesh, Meera / Saretzki, Gabriele / Hapangama, Dharani K

Biomedicines

2020 Volume 8, Issue 12

Abstract: Telomeres protect chromosomal ends and they are maintained by the specialised enzyme, telomerase. Endometriosis is a common gynaecological disease and high telomerase activity and higher hTERT levels associated with longer endometrial telomere lengths ... ...

Abstract	Telomeres protect chromosomal ends and they are maintained by the specialised enzyme, telomerase. Endometriosis is a common gynaecological disease and high telomerase activity and higher hTERT levels associated with longer endometrial telomere lengths are characteristics of eutopic secretory endometrial aberrations of women with endometriosis. Our ex-vivo study examined the levels of hTERC and DKC1 RNA and dyskerin protein levels in the endometrium from healthy women and those with endometriosis (
Language	English
Publishing date	2020-12-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines8120588
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Article: Telomerase and Telomeres in Endometrial Cancer.

Alnafakh, Rafah A A / Adishesh, Meera / Button, Lucy / Saretzki, Gabriele / Hapangama, Dharani K

Frontiers in oncology

2019 Volume 9, Page(s) 344

Abstract: Telomeres at the termini of human chromosomes are shortened with each round of cell division due to the "end replication problem" as well as oxidative stress. During carcinogenesis, cells acquire or retain mechanisms to maintain telomeres to avoid ... ...

Abstract	Telomeres at the termini of human chromosomes are shortened with each round of cell division due to the "end replication problem" as well as oxidative stress. During carcinogenesis, cells acquire or retain mechanisms to maintain telomeres to avoid initiation of cellular senescence or apoptosis and halting cell division by critically short telomeres. The unique reverse transcriptase enzyme complex, telomerase, catalyzes the maintenance of telomeres but most human somatic cells do not have sufficient telomerase activity to prevent telomere shortening. Tissues with high and prolonged replicative potential demonstrate adequate cellular telomerase activity to prevent telomere erosion, and high telomerase activity appears to be a critical feature of most (80-90%) epithelial cancers, including endometrial cancer. Endometrial cancers regress in response to progesterone which is frequently used to treat advanced endometrial cancer. Endometrial telomerase is inhibited by progestogens and deciphering telomere and telomerase biology in endometrial cancer is therefore important, as targeting telomerase (a downstream target of progestogens) in endometrial cancer may provide novel and more effective therapeutic avenues. This review aims to examine the available evidence for the role and importance of telomere and telomerase biology in endometrial cancer.
Language	English
Publishing date	2019-05-17
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2019.00344
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Article ; Online: Harmonisation of biobanking standards in endometrial cancer research.

Adishesh, M / Fyson, A / DeCruze, S B / Kirwan, J / Werner, H M J / Hapangama, D K

British journal of cancer

2017 Volume 117, Issue 4, Page(s) 485–493

Abstract: Background: Endometrial cancer is the most common gynaecological cancer and its incidence is predicted to escalate by 50-100% in 2025 with a parallel increase in associated mortality. Variations in the collection, processing and storage of biospecimens ... ...

Abstract	Background: Endometrial cancer is the most common gynaecological cancer and its incidence is predicted to escalate by 50-100% in 2025 with a parallel increase in associated mortality. Variations in the collection, processing and storage of biospecimens can affect the generalisability of the scientific data. We aimed to harmonise the collection of biospecimens, clinical data relevant to endometrial cancer and to develop standard operative procedures for the collection, processing and storage of endometrial cancer biospecimens. Methods: We designed research tools, which were evaluated and revised through three consensus rounds - to obtain local/regional, national and European consensus. Modified final tools were disseminated to a panel (n=40) representing all stakeholders in endometrial cancer research for consensus generation. Results: The final consensus demonstrated unanimous agreement with the minimal surgical and patient data collection tools. A high level of agreement was also observed for the other remaining standard tools. Conclusions: We here present the final versions of the tools, which are freely available and easily accessible to all endometrial cancer researchers. We believe that these tools will facilitate rapid progress in endometrial cancer research, both in future collaborations and in large-scale multicentre studies.
MeSH term(s)	Biomedical Research ; Consensus ; Endometrial Neoplasms/pathology ; Endometrial Neoplasms/surgery ; Female ; Guidelines as Topic ; Humans ; Specimen Handling/standards ; Surveys and Questionnaires ; Tissue Banks/standards
Language	English
Publishing date	2017-08-08
Publishing country	England
Document type	Consensus Development Conference ; Journal Article
ZDB-ID	80075-2
ISSN	1532-1827 ; 0007-0920
ISSN (online)	1532-1827
ISSN	0007-0920
DOI	10.1038/bjc.2017.194
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Article: Developing a Preoperative Algorithm for the Diagnosis of Uterine Leiomyosarcoma.

Lawlor, Hannah / Ward, Alexandra / Maclean, Alison / Lane, Steven / Adishesh, Meera / Taylor, Sian / DeCruze, Shandya Bridget / Hapangama, Dharani Kosala

Diagnostics (Basel, Switzerland)

2020 Volume 10, Issue 10

Abstract: Early diagnosis of the rare and life-threatening uterine leiomyosarcoma (LMS) is essential for prompt treatment, to improve survival. Preoperative distinction of LMS from benign leiomyoma remains a challenge, and thus LMS is often diagnosed post- ... ...

Abstract	Early diagnosis of the rare and life-threatening uterine leiomyosarcoma (LMS) is essential for prompt treatment, to improve survival. Preoperative distinction of LMS from benign leiomyoma remains a challenge, and thus LMS is often diagnosed post-operatively. This retrospective observational study evaluated the predictive diagnostic utility of 32 preoperative variables in 190 women who underwent a hysterectomy, with a postoperative diagnosis of leiomyoma (
Language	English
Publishing date	2020-09-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662336-5
ISSN	2075-4418
ISSN	2075-4418
DOI	10.3390/diagnostics10100735
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Article ; Online: Human Endometrial Carcinogenesis Is Associated with Significant Reduction in Long Non-Coding RNA, TERRA.

Adishesh, Meera / Alnafakh, Rafah / Baird, Duncan M / Jones, Rhiannon E / Simon, Shannon / Button, Lucy / Kamal, Areege M / Kirwan, John / DeCruze, S Bridget / Drury, Josephine / Saretzki, Gabriele / Hapangama, Dharani K

International journal of molecular sciences

2020 Volume 21, Issue 22

Abstract: Telomeres are transcribed as long non-coding RNAs called TERRAs (Telomeric repeat containing RNA) that participate in a variety of cellular regulatory functions. High telomerase activity (TA) is associated with endometrial cancer (EC). This study aimed ... ...

Abstract	Telomeres are transcribed as long non-coding RNAs called TERRAs (Telomeric repeat containing RNA) that participate in a variety of cellular regulatory functions. High telomerase activity (TA) is associated with endometrial cancer (EC). This study aimed to examine the levels of three TERRAs, transcribed at chromosomes 1q-2q-4q-10q-13q-22q, 16p and 20q in healthy (
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Carcinogenesis/genetics ; Carcinogenesis/metabolism ; Carcinogenesis/pathology ; Chromosomes, Human/genetics ; Chromosomes, Human/metabolism ; Endometrial Neoplasms/genetics ; Endometrial Neoplasms/metabolism ; Endometrial Neoplasms/pathology ; Endometrium/metabolism ; Endometrium/pathology ; Female ; Humans ; Male ; Middle Aged ; RNA, Long Noncoding/biosynthesis ; RNA, Long Noncoding/genetics ; RNA, Neoplasm/biosynthesis ; RNA, Neoplasm/genetics ; Telomere/genetics ; Telomere/metabolism ; Telomere/pathology ; Telomere Homeostasis ; Transcription, Genetic
Chemical Substances	RNA, Long Noncoding ; RNA, Neoplasm
Language	English
Publishing date	2020-11-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21228686
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Article ; Online: FARGO-360: a multi-disciplinary survey of practice and perspectives on provision of care for patients with frailty presenting with gynecological cancers in the UK and Ireland.

International journal of gynecological cancer : official journal of the International Gynecological Cancer Society

2022 Volume 32, Issue 7, Page(s) 924–930

Abstract: Objectives: Frailty has been associated with worse cancer-related outcomes for people with gynecological cancers. However, the lack of clear guidance on how to assess and modify frailty prior to instigating active treatments has the potential to lead to ...

Abstract	Objectives: Frailty has been associated with worse cancer-related outcomes for people with gynecological cancers. However, the lack of clear guidance on how to assess and modify frailty prior to instigating active treatments has the potential to lead to large variations in practice and outcomes. This study aimed to evaluate current practice and perspectives of healthcare practitioners on the provision of care for patients with frailty and a gynecological cancer. Methods: Data were collected via a questionnaire-based survey distributed by the Audit and Research in Gynecological Oncology (ARGO) collaborative to healthcare professionals who identified as working with patients with gynecological malignancies in the United Kingdom (UK) or Ireland. Study data were collected using REDCap software hosted at the University of Manchester. Responses were collected over a 16 week period between January and April 2021. Results: A total of 206 healthcare professionals (30 anesthetists (14.6%), 30 pre-operative nurses (14.6%), 51 surgeons (24.8%), 34 cancer specialist nurses (16.5%), 21 medical/clinical oncologists (10.2%), 25 physiotherapists/occupational therapists (12.1%) and 15 dieticians (7.3%)) completed the survey. The respondents worked at 19 hospital trusts across the UK and Ireland. Frailty scoring was not routinely performed in 63% of care settings, yet the majority of practitioners reported modifying their practice when providing and deciding on care for patients with frailty. Only 16% of organizations surveyed had a dedicated pathway for assessment and management of patients with frailty. A total of 37% of respondents reported access to prehabilitation services, 79% to enhanced recovery, and 27% to community rehabilitation teams. Conclusion: Practitioners from all groups surveyed considered that appropriate training, dedicated pathways for optimization, frailty specific performance indicators and evidence that frailty scoring had an impact on clinical outcomes and patient experience could all help to improve care for frail patients.
MeSH term(s)	Female ; Frailty/epidemiology ; Frailty/therapy ; Genital Neoplasms, Female/therapy ; Humans ; Ireland/epidemiology ; Surveys and Questionnaires ; Triallate ; United Kingdom/epidemiology
Chemical Substances	Triallate (A9S097HS99)
Language	English
Publishing date	2022-07-04
Publishing country	England
Document type	Journal Article
ZDB-ID	1070385-8
ISSN	1525-1438 ; 1048-891X
ISSN (online)	1525-1438
ISSN	1048-891X
DOI	10.1136/ijgc-2022-003396
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